Abstract
Cardiopulmonary bypass (CPB) may cause acute lung injury leading to increased morbidity and mortality after cardiac surgery. Preconditioning by inhaled carbon monoxide reduces pulmonary inflammation during CPB. We hypothesized that inhaled carbon monoxide mediates its anti-inflammatory and cytoprotective effects during CPB via induction of pulmonary heat shock proteins (Hsps). Pigs were randomized either to a control group, to standard CPB, to carbon monoxide+CPB, or to quercetin (a flavonoid and unspecific inhibitor of the heat shock response)+control, to quercetin+CPB, and to quercetin+carbon monoxide+CPB. In the carbon monoxide groups, lungs were ventilated with 250 ppm carbon monoxide in addition to standard ventilation before CPB. At various time points, lung biopsies were obtained and pulmonary Hsp and cytokine concentrations determined. Haemodynamic parameters were largely unaffected by CPB, carbon monoxide inhalation, or administration of quercetin. Compared with standard CPB, carbon monoxide inhalation significantly increased the pulmonary expression of the Hsps 70 [27 (SD 3) vs 69 (10) ng ml(-1) at 120 min post-CPB, P<0.05] and 90 [0.3 (0.03) vs 0.52 (0.05) after 120 min CPB, P<0.05], induced the DNA binding of heat shock factor-1, reduced interleukin-6 protein expression [936 (75) vs 320 (138) at 120 min post-CPB, P<0.001], and decreased CPB-associated lung injury (assessed by lung biopsy). These carbon monoxide-mediated effects were inhibited by quercetin. As quercetin, a Hsp inhibitor, reversed carbon monoxide-mediated pulmonary effects, we conclude that the anti-inflammatory and protective effects of preconditioning by inhaled carbon monoxide during CPB in pigs are mediated by an activation of the heat shock response.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.